EASTBIO: Monoclonal antibodies targeting the fungal cell surface: next generation antifungal therapeutics at Aberdeen University on FindAPhD.com

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Prof C Munro, Dr D van Aalten, Dr S Palliyil No more applications being accepted Competition Funded PhD Project (UK Students Only)

Aberdeen United Kingdom Biochemistry Bioinformatics Immunology Microbiology Molecular Biology Structural Biology

About the Project

Supervisors:

Professor Carol Munro - University of Aberdeen, Institute of Medical Sciences - [Email Address Removed]

Professor Daan Van Aalten - School of Life Sciences, University of Dundee - [Email Address Removed]

Dr Soumya Palliyil - University of Aberdeen, Scottish Biologics Facility - [Email Address Removed]

Fungal pathogens of Candida and Aspergillus species cause life-threatening invasive fungal infections that can be recalcitrant to antifungal therapy. There is a clear clinical need for novel antifungal therapies. The fungal cell wall contains virulence factors and mediates interactions with the host. In a targeted approach we have engineered recombinant monoclonal antibodies that recognise cell wall proteins of fungal pathogens. These antibodies have huge potential to accurately diagnose and treat fungal infections. This PhD project will extensively characterise the binding interactions of our lead antibodies using heterologously expressed cell surface proteins, short peptide sequences, and fungal cells from different clinical isolates. At the University of Dundee, the Van Aalten lab has elucidated the structure of several fungal-specific cell surface proteins and will provide expertise in the expression of fungal glycoproteins that will be utilised for the characterisation of antibody binding using biochemical assays (ELISAs) and Surface Plasmon Resonance (SPR). In addition, they can provide expertise in protein crystallography to elicit antibody binding to the fungal targets and in silico construction of the 3D structure of these antibodies and target proteins to study the macromolecular interactions through interface predictions and molecular docking. The student will also receive advanced training in antibody engineering at the Scottish Biologics Facility, headed by Dr Soumya Palliyil. Using the latest tools in protein engineering and combining the expertise of recombinant antibody development, this project will also explore the feasibility of generating bispecific formats of the existing antibodies e.g. two different antigen binding arms on the same antibody molecule or potent antibody drug conjugates (ADCs) by biochemically coupling an antimicrobial agent to the selected lead antibody for enhanced pathogen killing.

It may be possible to undertake this project part-time, in discussion with the lead supervisor.

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Application Procedure:

Please visit this page for full application information: BBSRC EASTBIO Doctoral Training Partnership Studentship | The School of Medicine, Medical Sciences and Nutrition | The University of Aberdeen (abdn.ac.uk)

Please send your completed EASTBIO application form, along with academic transcripts to Alison Innes at [Email Address Removed]

Two references should be provided by the deadline using the EASTBIO reference form.

Please advise your referees to return the reference form to [Email Address Removed]

Unfortunately due to workload constraints, we cannot consider incomplete applications

Funding Notes

This 4 year PhD project is part of a competition funded by EASTBIO BBSRC Doctoral Training Partnership.
This opportunity is open to home/UK candidates (including EU nationals that hold UK settled or pre-settled status) and provides funding to cover a stipend and tuition fees. Please refer to UKRI website and Annex B of the UKRI Training Grant Terms and Conditions for full eligibility criteria.
Candidates should have (or expect to achieve) a minimum of a 2:1 UK Honours degree, or the equivalent qualifications gained outside the UK, in a relevant subject.

References

1) Ibe, C and Munro, CA (2021) Fungal cell wall: An underexploited target for antifungal therapies. PLoS Pathog 17(4):e1009470. doi: 10.1371/journal.ppat.1009470.
2) Molecular mechanisms of yeast cell wall glucan remodeling. Hurtado-Guerrero R, Schüttelkopf AW, Mouyna I, Ibrahim AF, Shepherd S, Fontaine T, Latgé JP, van Aalten DM. J Biol Chem. 2009 Mar 27;284(13):8461-9
3) Mechanisms of redundancy and specificity of the Aspergillus fumigatus Crh transglycosylases.
Fang W, Sanz AB, Bartual SG, Wang B, Ferenbach AT, Farkaš V, Hurtado-Guerrero R, Arroyo J, van Aalten DMF. Nat Commun. 2019 Apr 10;10(1):1669.